Large polyfunctional molecules such as proteins have the potential for forming a variety of derivatives of the original product. Indeed, modifications such as glycosylations and .gamma.-carboxylations are well known and have been shown to have important physiological roles. Other modifications arise from the purification process. Degradation products also arise during storage of the protein. It is impossible a priori to know whether these structures will or will not have biological activity in their own right or the level and kind, if any, of such activity. Derivatives of pituitary derived human growth hormone (hGH) have been reported in the literature. Different size isomers of hGH have been detected in the plasma of both normal and acromegalic individuals. The predominant size isomer, the 22,000 dalton monomer, has been detected in several derivatized forms, including three proteolytically modified forms [Chramback, A., Yadley, R. A., Ben-David, M., and Rodbard, D. (1973) Endocrinology 93, 848-857; Singh, R. N. P., Seavey, B. K., Rice, V. P., Lindsey, T. T., and Lewis, U. J. (1974) Endocrinology 94, 883-891], an acetylated form and two deamidated forms [Lewis, U. J., Singh, R. N. P., Bonewald, L. F., Lewis, L. J., and Vanderlaan, W. P. (1979) Endocrinology 104, 1256-1265; Lewis, U. J., Singh, R. N. P., Bonewald, L. F., and Seavey, B. K. (1981) J. Biol. Chem. 256, 11645-11650]. Other hGH derivatives have been detected but have not been characterized. The recent use of recombinant DNA techniques to mass produce proteins of pharmaceutical interest has made it possible to attempt to prepare specifically modified products of the native recombinantly produced materials.
The availability of human growth hormone enabled us to discover and develop a method for producing a novel monosulfoxide derivative of human growth hormone, and it is to such derivative that this invention is directed. The compound of this invention is the sulfoxide of human growth hormone in which, of the three available methionine residues, the residue at position 14 is alone oxidized to its corresponding sulfoxide. For convenience, the compound of this invention is designated Met(O).sup.14 -human growth hormone, or Met(O).sup.14 -hGH. The compound of this invention unexpectedly exhibits a potency approximately equivalent to that of hGH itself.